Omega-3 Fatty Acids in Critical Illness: Mechanisms and Clinical ... · lists fatty acids in foods...

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Omega-3 Fatty Acids in Critical Illness:

Mechanisms and Clinical Applications:

When disease is prevented,

treatment costs are not needed

Bill Lands, PhD

Fellow AAAS, ASN, SFRBM

My initial research on humans was funded by an

unrestricted award from Pfizer Inc.

I am a stockholder and non-employee member of the board

of directors of Omega Protein Inc.

Nutrition Support Therapy is part of

nutrition therapy which is a component of

medical treatment that can include

oral, enteral, and parenteral nutrition

to maintain or restore

optimal nutrition status

and health.

Clinical Effects Incorporation & Washout

Balance in the Tissue is the Issue

BS vanderMeij et al, Am.J.Clin.Nutr. 2011; 94: 1248-1265

Found = 2921 Enteral Parenteral

1146 1775

“Potential” studies 93 98

RCTs included 14 14

Found = 5111 Enteral Parenteral

2309 2802

“Potential” studies 171 72

Studies included 27 9

Concluded beneficial effects of n-3FA supplementation

See also meta-analysis of parachutes:

GCS Smith and JP Pell, Brit Med J. 2003; 327: 1459

Know Your Numbers

OPTIMAL NUTRITION STATUS means:

much chronic disease prevented

many treatments not needed

Know Their Context

1. Your food’s Omega-3 Balance Scores

2. Your blood’s %omega 3 in HUFA

3. Your annual healthcare claim costs

USDA Nutrient Database

lists fatty acids in foods

Finger-tip blood-spot assay

lists fatty acids in blood

Use 11 n-3 & n-6 acids

to form one value of

Omega-3 Balance Score

Use 8 n-3 & n-6 HUFA

to form one value of

%Omega-3 in HUFA

14:0 1.30 0.20 Myristic 14:0 1.30 0.20 Myristic

14:1 1.59 0.05 Myristoleic 14:1 1.59 0.05 Myristoleic

15:0 2.37 0.18 Pentadecanoic 15:0 2.37 0.18 Pentadecanoic

15:1 0.34 0.09 15:1 0.34 0.09

16:0 23.41 21.05 Palmitic 16:0 23.41 21.05 Palmitic

16:1w5 0.00 0.08 16:1w5 0.00 0.08

16:1w7 2.30 0.70 Palmitoleic 16:1w7 2.30 0.70 Palmitoleic

17:0 0.00 0.21 Heptadecanoic 17:0 0.00 0.21 Heptadecanoic

17:1 0.00 0.62 17:1 0.00 0.62

18:0 9.05 12.53 Stearic 18:0 9.05 12.53 Stearic

18:1w9 17.96 8.87 Oleic 18:1w9 17.96 8.87 Oleic

18:1w7 0.00 2.24 Vaccenic 18:1w7 0.00 2.24 Vaccenic

18:1w5 0.00 0.35 18:1w5 0.00 0.35

18:2w6 27.08 23.90 Linoleic (LA) 18:2w6 27.08 23.90 Linoleic (LA)

18:3w6 0.32 0.12 gamma-linolenic (GLA) 18:3w6 0.32 0.12 gamma-linolenic (GLA)

18:3w3 0.74 0.21 alpha-linolenic (ALA) 18:3w3 0.74 0.21 alpha-linolenic (ALA)

18:4w3 0.00 0.10 Stearidonic (SDA) 18:4w3 0.00 0.10 Stearidonic (SDA)

20:0 0.00 0.33 Arachidic 20:0 0.00 0.33 Arachidic

20:1w9 0.00 0.04 20:1w9 0.00 0.04

20:1w7 0.00 0.22 20:1w7 0.00 0.22

20:2w6 0.60 0.47 Eicosadienoic 20:2w6 0.60 0.47 Eicosadienoic

20:3w9 0.31 0.13 Mead's acid 20:3w9 0.31 0.13 Mead's acid

20:3w6 1.55 3.41 Dihomogammalinolenic (DGLA) 20:3w6 1.55 3.41 Dihomogammalinolenic (DGLA)

20:4w6 6.43 12.81 Arachidonic (AA) 20:4w6 6.43 12.81 Arachidonic (AA)

20:3w3 0.00 0.07 Eicosatrienoic (n-3) 20:3w3 0.00 0.07 Eicosatrienoic (n-3)

20:4w3 0.00 0.04 Eicosatetraenoic (n-3) 20:4w3 0.00 0.04 Eicosatetraenoic (n-3)

20:5w3 0.36 0.59 Eicosapentaenoic (EPA) 20:5w3 0.36 0.59 Eicosapentaenoic (EPA)

22:0 0.62 1.11 Behenic 22:0 0.62 1.11 Behenic

22:1w9 0.34 0.01 Erucic 22:1w9 0.34 0.01 Erucic

22:4w6 0.97 0.76 Docosatetraenoic 22:4w6 0.97 0.76 Docosatetraenoic

22:5w6 0.66 0.60 Docosapentaenoic (n-6) 22:5w6 0.66 0.60 Docosapentaenoic (n-6)

22:5w3 0.44 1.13 Docosapentaenoic (n-3) 22:5w3 0.44 1.13 Docosapentaenoic (n-3)

24:0 0.00 0.88 Lignoceric 24:0 0.00 0.88 Lignoceric

22:6w3 1.03 3.59 Docosahexaenoic (DHA) 22:6w3 1.03 3.59 Docosahexaenoic (DHA)

Chicken

Coho salmon

Turkey

- 10.9

Omega-3 Balance Scores

Beef steak

+ 30.6

http://www.fastlearner.org/Omega-3Balance.htm

Highly Unsaturated Fatty Acids (HUFA)

have 20- and 22-carbons & 3 or more double bonds

Linolenic acid (18:3n-3) ALA Linoleic acid (18:2n-6) LA

OMEGA-3 OMEGA-6

Eicosapentaenoic (20:5n-3)EPA Arachidonic acid (20:4n-6) AA

Docosahexaenoic (22:6n-3) DHA DPA (22:5n-6)

Dihomoγlinolenate (20:3n-6) DGLA

DPA (22:5n-3) Adrenic Acid (22:4n-6)

From Vitamins to Hormones: Competition is the Context

Stearidonic acid (18:4n-3) Gamma-linolenic acid (18:3n-6)

HUFA make hormones

Every year excess actions of omega-6 at tissue receptors cause

financial loss for people & corporations & the nation

Medical &

Pharmacy cost

Health-related Absenteeism

& Presenteeism loss

with an

Overall loss =

$5,184

$10,000

employee 10 thousand

employees

$51,840,000

>millions

$2,250,000,000,000

>trillions $15,200

150 million

employees

$152,000,000

>millions

$777,000,000,000

>billions

If we can prevent half of this, why don’t we?

When disease is prevented, treatment costs are not needed

amino acids

nucleosides

fatty acids

sugars

essential FA

oxidant stress &

inflammation &

proliferation &

impaired nitric oxide

% n-6 in HUFA of

tissue phospholipids

n-3 & n-6 HUFA release

XS n-6 eicosanoids

vessel wall

plaques

thrombosis

ischemia

arrhythmia

Morbidity &

Mortality

platelet activation

aspirin

Biomarker <<This is a valid surrogate endpoint for nutrition-based

primary prevention of CHD morbidity & mortality

Connecting the primary cause

to its consequences

arthritis

asthma

colon cancer

length of hospital stay

psychiatric disorders

workplace disruption

health care $$ claims

We store vitamin-like omega-3 and omega-6 acids as hormone

precursors (HUFA) that form hormones acting on tissue receptors

<<Omega-3 Balance Score average

Wada et al., J Biol Chem. 2007; 282(31):: 22254-66.

Relative n-3 & n-6

actions with

enzymes & receptors

Overall,

n-3 forms act

less intensely

than n-6 forms.

Release HUFA

Oxidize HUFA

to intermediates

Make hormones

Hormone

receptor

actions

Tissue HUFA Eicosanoids

Differ

Anything 3 can

I can do better!

Good grief!

Sometimes 6 is just too

http://efaeducation.nih.gov/sig/beginners.html

CHD Mortality and Tissue HUFA

y = 3.0323x - 74.8

R2 = 0.9866

20 30 40 50 60 70 80

% n-6 HUFA in Total HUFA

Greenland

Quebec Inuit

Quebec Cree

Quebec Urban

When disease is prevented, treatment costs are not needed.

Americans have high omega-6 in HUFA & an omega-3 deficit

% omega-6 in HUFA

= MRFIT

quintiles

Relative risk - -

Siscovick,1995

Alberts, 2002

$2,076/yr

$3,930/yr

$3,052/yr

WV-PEIA=$6,408

Health Claim Cost

USA=$5,184/yr

Foods in North America have an excess of n-6 over n-3 fats - -

- - - and cause accumulation of a high percent of n-6 in HUFA.

location %HUFA %6inH

Detroit - 2009 19 78

Baltimore-2008 24 79

Quebecer-2001 8 78

ARIC study-2007 15 77

Detroit-2005 12 82

Columbus, 2007 13 87

avg. = 15 80

location %HUFA %6inH

Detroit - 2009 19 78

Baltimore-2008 24 79

Quebecer-2001 8 78

ARIC study-2007 15 77

Detroit-2005 12 82

Columbus, 2007 13 87

avg. = 15 80

+3 +2 +1 0 -1 -2 -3 -4 -5 -6 -7 -8

Related %omega6 in HUFA

Diverse Food Habits and Tissue Consequences

72% 67% 62% 57% 52% 47% 42% 37% 32% 27% 22% 17% 12%

28% 33% 38% 43% 48% 53% 58% 63% 68% 73% 78% 83% 88%

Average daily menu balance

Blood Assay value Likely Likely daily average Blood Assay value Likely Likely daily average

Team %n-3inH food habit Omega-3 Balance Score Team %3inH food habit Omega-3 Balance Score

Member February data Member May data

G 52 typical 0 Related Health G 67 traditional 2

P 50 middle-aged -1 Claim Cost P 64 Japanese 2 Related Health

I 48 Japanese -1 $ ???? I 55 0 Claim Cost

L 44 -2 A 51 -1

J 34 typical -4 $2,076 L 51 typical -1

O 33 Mediterranian -4 O 50 middle-aged -1

H 30 -5 $3,052 Y 47 Japanese -1 $ ????

C 29 -5 H 41 -2

N 26 typical -5 R 40 -3

A 25 European -5 $3,930 V 40 -3

V 25 -5 T 39 -3 $2,076

W 23 -6 F 38 -3

S 22 typical -6 J 37 -3

E 22 American -6 $5,184 K 36 -3

U 21 -6 N 35 typical -4 $3,052

Q 21 -6 S 30 Mediterranian -4

X 19 typical -7 W 27 -5

K 17 West -7 $6,408 B 27 typical -5 $3,930

B 16 Virginian ? -7 E 26 European -5

M 16 -7 M 25 -5

D 15 -7 U 25 -5

F 15 -7 D 23 -6 $5,184

Y 15 -7 Q 22 typical -6

R 15 -7 X 21 American -6

T 12 -8 C 21 -6

$6,408

We started with lots of -7 values - - - We changed to lots of -3

http://www.fastlearner.org/pdfs/Eat3.pdf

http://www.fastlearner.org/pdfs/Nix6.pdf

Chicken

Coho salmon

Turkey

- 10.9

Omega-3 Balance Scores

Beef steak

+ 30.6

Oatmeal

Barley

Quinoa

Buckwheat

Kellog’s Corn Flakes

Flax meal

+ 28.1

+3 +2 +1 0 -1 -2 -3 -4 -5 -6 -7 -8

Diverse Food Habits and Tissue Consequences

28% 33% 38% 43% 48% 53% 58% 63% 68% 73% 78% 83% 88%

Average daily menu balance

Parenteral Foods and Their Balance Scores

Omegaven (10%) + 49 Lipoven (10%) - 9

Lipoplus (20%) + 7 Intralipid (20%) - 20

Tools for Primary Prevention

Low-cost assay of %n-6 in HUFA

to monitor risk and compliance

Known diet-tissue relationship

to predict food impacts

Computer-aided food choice

to counsel good food combinations

Effective Primary Prevention Needs You

TO UNDERSTAND–

Food energy causes transient tissue insults

Omega-6 hormones amplify insults into inflamed injuries

Omega-3 HUFA diminish inflammatory insults

TO TEACH -

EAT FEWER CALORIES PER MEAL

EAT LESS OMEGA-6

EAT MORE OMEGA-3

When disease is prevented,

treatment costs are not needed

No prescription needed to:

Clinical trials using

indirect biomarkersConnecting primary cause

to consequences

ACCORD

ADVANCE

VA-Diabetes

ENHANCE

Also CRP

amino acids

nucleosides

fatty acids

sugars

essential FA

acetyl-CoA malonyl-CoA

Fatty acyl-CoA

HMG-CoA

mevalonate

isoprenoids

prenylated proteins

cholesterol

oxidant stress &

inflammation &

proliferation &

impaired NO

FFA + LDLcholesterol

Triglyceridemia

Obesity

Insulin resistance

Elevated glucose

vessel wall

plaques

thrombosis

ischemia

arrhythmia

Morbidity &

Mortality

platelet activation

statinBiomarkers

Excess food energy

causes transient insults

with every meal

squalene

% n-6 in HUFA of

XS n-6 hormones

aspirin

Biomarker

amino acids

nucleosides

fatty acids

sugars

essential FA

acetyl-CoA malonyl-CoA

Fatty acyl-CoA

HMG-CoA

mevalonate

isoprenoids

prenylated proteins

cholesterol

oxidant stress &

inflammation &

proliferation &

impaired NO

FFA + LDLcholesterol

Triglyceridemia

Obesity

Insulin resistance

Elevated glucose

vessel wall

plaques

thrombosis

ischemia

arrhythmia

Morbidity &

Mortality

platelet activation

statinBiomarkers

Excess food energy

causes transient insults

with every meal

squalene

% n-6 in HUFA of

XS n-6 hormones

aspirin

Biomarker

Jupiter

CO2 O2

+ electrons ADP work

H2O exercise

ATP synthesize

CO2 O2

+ electrons ADP work

H2O exercise

ATP synthesize

1.- Defining and Filling Practice Gaps (esp. data transfer and attitudes)

- Recognize selective eicosanoid receptors are in nearly every cell and tissue

- Know the chain of events connecting vitamin>>hormone>>disease

- Raise priority of causal mediators over mere associated/predictive risk factors

- Know more of current %n-6 in HUFA status and preventable healthcare costs

- Prevent the cause of signs – do not just suppress signs and symptoms

- Discuss preventable financial losses with patients, families and CEOs

- Implement primary prevention

-Stop silo mentality that prevents constructive feedback of information

2.- Encourage new tools to monitor and manage causal mediators of wellness

- Faster, cheaper, high-throughput assays of HUFA proportions in individuals

- Simple “apps” for informed decisions on foods, supplements & nutraceuticals

American College of Nutrition – 52nd Meeting, Nov.19, 2011

“Clinical Nutrition as Core Medicine”

Paradoxes in current advice to the public

Lands, Prog.Lipid Res. 2008; 47: 77-106.

Good medical practice will –

- - Remove a preventable cause of disease

not just a sign or symptom produced by the cause

- - Use biomarkers that monitor causal connections

- - Know that NOT all predictive risk factors cause disease

and we should not over-interpret associations!

- - Know explicit contexts for terms being used.

“Continuing preventable disease” - is a paradox

due to neglected information and imprecise terms

Omega-3 Fatty Acids in Critical Illness: Mechanisms and Clinical ... · lists fatty acids in foods...

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